The progesterone receptor (PR) exists as two isoforms, PRA and PRB. In vitro studies have shown that these proteins are functionally distinct, suggesting that their relative expression can influence progesterone response. Low-grade endometrial stromal sarcoma (LGESS) is an uncommon tumor that usually expresses PR. In normal endometrial stroma, both PR isoforms are present with PRA predominant throughout the menstrual cycle. The relative expression of PRA and PRB in LGESS has not been previously reported. All nine cases of primary LGESS (seven uterine, two extrauterine) expressed PRB. Eight tumors also contained PRA and it was the predominant isoform in seven cases. These tumors had similar histopathologic appearances, whereas a case with approximately equal PR isoform expression showed features of sex cord or smooth muscle differentiation. An extrauterine tumor expressing only PRB had myxoid stroma. Recurrent tumor in two cases, which expressed predominantly PRA in the primary, contained reduced levels of PR consisting predominantly or entirely of PRB after prolonged interval progestin therapy. Most primary LGESSs showed PR isoform expression similar to normal endometrial stroma, consistent with the highly differentiated phenotype of this tumor. Variant differentiation or disease recurrence was accompanied by an altered PR isoform profile that could impact on hormone response.